Homology Search Tools

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Homology Search Tools

• Kun-Mao Chao (???)
• Department of Computer Science and Information
  Engineering
• National Taiwan University, Taiwan
• WWW http//www.csie.ntu.edu.tw/kmchao

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Homology Search Tools

• Smith-Waterman(Smith and Waterman, 1981
  Waterman and Eggert, 1987)
• FASTA(Wilbur and Lipman, 1983 Lipman and
  Pearson, 1985)
• BLAST(Altschul et al., 1990 Altschul et al.,
  1997)
• BLAT(Kent, 2002)
• PatternHunter(Li et al., 2004)

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Finding Exact Word Matches

• Hash Tables
• Suffix Trees
• Suffix Arrays

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Hash Tables
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Suffix Trees (I)
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Suffix Trees (II)
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Suffix Arrays
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FASTA

1. Find runs of identities, and identify regions
   with the highest density of identities.
2. Re-score using PAM matrix, and keep top scoring
   segments.
3. Eliminate segments that are unlikely to be part
   of the alignment.
4. Optimize the alignment in a band.

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FASTA
Step 1 Find runes of identities, and identify
regions with the highest density of identities.
Sequence B
Sequence A
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FASTA
Step 2 Re-score using PAM matrix, andkeep top
scoring segments.
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FASTA
Step 3 Eliminate segments that are unlikely to
be part of the alignment.
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FASTA
Step 4 Optimize the alignment in a band.
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BLAST

• Basic Local Alignment Search Tool(by Altschul,
  Gish, Miller, Myers and Lipman)
• The central idea of the BLAST algorithm is that a
  statistically significant alignment is likely to
  contain a high-scoring pair of aligned words.

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The maximal segment pair measure

• A maximal segment pair (MSP) is defined to be the
  highest scoring pair of identical length segments
  chosen from 2 sequences.(for DNA Identities
  5 Mismatches -4)

• The MSP score may be computed in time
  proportional to the product of their lengths.
  (How?) An exact procedure is too time consuming.
• BLAST heuristically attempts to calculate the MSP
  score.

the highest scoring pair
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A matrix of similarity scores
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A maximum-scoring segment
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BLAST

• Build the hash table for Sequence A.
• Scan Sequence B for hits.
• Extend hits.

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BLAST
Step 1 Build the hash table for Sequence A.
(3-tuple example)
For protein sequences Seq. A ELVISAdd xyz to
the hash table if Score(xyz, ELV) ? TAdd
xyz to the hash table if Score(xyz, LVI) ?
TAdd xyz to the hash table if Score(xyz,
VIS) ? T
For DNA sequences Seq. A AGATCGAT
12345678 AAAAAC..AGA 1..ATC 3..CGA
5..GAT 2 6..TCG 4..TTT

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BLAST
Step2 Scan sequence B for hits.
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BLAST
Step2 Scan sequence B for hits.
Step 3 Extend hits.
BLAST 2.0 saves the time spent in extension, and
considers gapped alignments.
hit
Terminate if the score of the sxtension fades
away. (That is, when we reach a segment pair
whose score falls a certain distance below the
best score found for shorter extensions.)
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Gapped BLAST (I)
The two-hit method
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Gapped BLAST (II)
Confining the dynamic-programming
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BLAT
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PatternHunter (I)
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PatternHunter (II)
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Remarks

• Filtering is based on the observation that a good
  alignment usually includes short identical or
  very similar fragments.
• The idea of filtration was used in FASTA, BLAST,
  BLAT, and PatternHunter.